From the European Genetic Database (EUGENDA,
www.eugenda.org), clinical, genetic, and imaging data of 1878 individuals were reviewed. Patients and controls were recruited from a small area around Cologne, in Western Germany. Recruitment was initiated by participants and was not “hospital-based.” The study was performed in accordance with the tenets of the Declaration of Helsinki and the Medical Research Involving Human Subjects Act (WMO) and was approved by the local ethics committee. Written informed consent was obtained from all participants.
Patient data included age (subdivided into 8 groups: 50–60 years, 61–65 years, 66–70 years, 71–75 years, 76–80 years, 81–85 years, 86–90 years, and >90 years), sex (female/male), BMI (subdivided in three groups: normal: <25, overweight 25–29.99 and obese ≥30), marital status (living alone/living together), highest education level (no school degree or elementary school, high school, professional education, university degree), and iris color (light [blue, gray], medium [green, hazel], dark [brown]). Medical history was obtained by an interviewer-assisted questionnaire and included arterial hypertension, myocardial infarction, angina pectoris, stroke or transient ischemic attack (TIA), congestive heart failure, vascular bypass surgery, other heart disease, blood-clotting disorder, diabetes, rheumatoid arthritis, thyroid disease, cancer, liver disease, kidney disease, lung disease, migraine, and history of allergy (including all types of allergies, but primarily pollen allergy and house dust mite allergy). Furthermore, data about the use of platelet inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), antihypertensive drugs, antidiabetic drugs, corticosteroids, coumarin derivates, and antiglaucomatous drugs was evaluated (yes/no). Data of the lifestyle factors smoking (never/ever); regular alcohol use (yes/no); regular (at least once a week) intake of fruit, vegetables, fish, red meat, and physical exercise; and past sunlight exposure (more or less than 8 hours outside activity per day during working life).
For a validated environmental risk model, the dataset was randomly subdivided into a training set, containing two-thirds of cases and a validation set containing one-third of cases.
All cases were included that either were controls or had neovascular AMD (nAMD). Staging of AMD was performed by grading of retinal images, including stereo color fundus photographs (FPs) and, if available, fluorescein angiograms (FAs, available in 40% of cases) and spectral domain optical coherence tomograms (SDOCTs, available in 81% of cases), according to the standard protocol of the Cologne Image Reading Center by certified graders (TR, LE). Patients without drusen and patients having only small drusen (<63 μm) or pigmentary changes and fewer than 10 small drusen were defined as controls. Neovascular AMD was classified as CNV secondary to AMD in at least one eye. Choroidal neovascularization was termed as choroidal neovascular lesion within the Early Treatment Diabetic Retinopathy Study grid on FPs, Fas, or SDOCTs, when there was evidence for fluid, blood, or fibrovascular tissue on FPs, active classic or occult CNV, or signs for previous CNV, such as staining scar on FAs and/or retinal or subRPE fluid and/or tissue on SDOCT.